Details

Autor(en) / Beteiligte

• Nguyen, Tan A.
• Smith, Blake R.C.
• Tate, Michelle D.
• Belz, Gabrielle T.
• Barrios, Marilou H.
• Elgass, Kirstin D.
• Weisman, Alexandra S.
• Baker, Paul J.
• Preston, Simon P.
• Whitehead, Lachlan
• Garnham, Alexandra
• Lundie, Rachel J.
• Smyth, Gordon K.
• Pellegrini, Marc
• O’Keeffe, Meredith
• Wicks, Ian P.
• Masters, Seth L.
• Hunter, Craig P.
• Pang, Ken C.

Titel

SIDT2 Transports Extracellular dsRNA into the Cytoplasm for Innate Immune Recognition

Ist Teil von

• Immunity (Cambridge, Mass.), 2017-09, Vol.47 (3), p.498-509.e6

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Double-stranded RNA (dsRNA) is a common by-product of viral infections and acts as a potent trigger of antiviral immunity. In the nematode C. elegans, sid-1 encodes a dsRNA transporter that is highly conserved throughout animal evolution, but the physiological role of SID-1 and its orthologs remains unclear. Here, we show that the mammalian SID-1 ortholog, SIDT2, is required to transport internalized extracellular dsRNA from endocytic compartments into the cytoplasm for immune activation. Sidt2-deficient mice exposed to extracellular dsRNA, encephalomyocarditis virus (EMCV), and herpes simplex virus 1 (HSV-1) show impaired production of antiviral cytokines and—in the case of EMCV and HSV-1—reduced survival. Thus, SIDT2 has retained the dsRNA transport activity of its C. elegans ortholog, and this transport is important for antiviral immunity. [Display omitted] •SIDT2 is in endo-lysosomes and interacts with internalized double-stranded RNA•SIDT2 promotes escape of endosomal dsRNA and cytoplasmic RLR signaling•During HSV-1 infection, RLR signaling in bystander cells requires SIDT2•Loss of SIDT2 impairs IFN-β production and survival after HSV-1 and EMCV infection Extracellular double-stranded RNA is predominantly sensed by cytosolic RLRs after endocytic uptake, but how it enters the cytoplasm is unknown. Nguyen and colleagues demonstrate that the endo-lysosomal protein SIDT2 transports double-stranded RNA into the cytoplasm for RLR signaling and is required for survival after EMCV infection.